EVALUATING THE ENDOCRINE DISRUPTING COMPOUND PERFLUOROOCTANOIC ACID IN AN EXPERIMENTAL MODEL OF ENDOMETRIOSIS

INTRODUCTION AND OBJECTIVES: Endometriosis is a gynecologic, multifactorial, estrogen-dependent disease characterized by the presence of glands and stroma outside the uterine cavity. Although it is a benign disease, it has similarities to malignant cells. Perfluorooctanoic acid (PFOA), an endocrine disruptor widely distributed in the environment, has been classified as a Group 1 human carcinogen by the International Agency for Research on Cancer. In addition to disrupting molecular pathways related to reproductive hormones and their receptors, it is also associated with increased reactive oxygen species (ROS). Therefore, the study was designed to evaluate the effects of oral exposure to PFOA on inflammatory, angiogenic, and oxidative stress pathways in an endometriosis model. MATERIAL AND METHODS: Eighteen female Wistar rats (8 weeks old, 150-200 g), randomized into four groups after autologous endometrial implantation, were exposed to PFOA (5 mg.kg-1) via gavage for 14 or 42 days, under CEUA UEZO approval (009/2019). After treatment, blood (leukogram, glycemia, biochemistry, estrogen and progesterone) and endometriotic lesions (macroscopic, histologic and immunohistochemical) were collected for analysis. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), reduced glutathione (GSH), lipid peroxidation (LPO) and protein carbonylation (PTC), and the expression of VEGF, MMP-2, MMP-9, PTGES2 and KDR genes were measured in endometriotic lesions, brain and liver. RESULTS AND CONCLUSION: Exposure to PFOA has been shown to cause significant physiological and biochemical changes. Increases in estrogen, VEGF gene expression, and endometriotic lesion weight were observed. Immunologic effects such as lymphocytopenia, monocytopenia, neutrophil hypersegmentation, presence of blasts and increase in C-reactive protein (CRP) levels were observed. Changes in lipoprotein levels, including cholesterol, LDL, HDL, and triglycerides, possibly mediated by PPARY activation, were observed. Markers of liver injury such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were elevated. An increase in CAT levels and a decrease in brain and liver GSH levels were observed, possibly associated with a reduction in antioxidant capacity. As a biomarker of oxidative stress, liver LPO levels were reduced, with no significant difference for PTC. These results suggest that exposure to PFOA directly affects angiogenic, inflammatory, immunobiological, hepatic and oxidative processes, contributing to the mechanisms underlying the pathogenesis of the disease, in addition to enhancing its carcinogenic potential by promoting an ideal environment for growth and proliferation of cellular damage, as well as predisposition to cellular and genetic damage.